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Open data
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Basic information
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Title | Endogenous ligand bound FLVCR1 | |||||||||
![]() | Endogenous ligand bound FLVCR1 | |||||||||
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![]() | Choline / ethanolamine / membrane transport / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() heme export / heme transport / heme transmembrane transporter activity / embryonic skeletal system morphogenesis / head morphogenesis / regulation of organ growth / Heme biosynthesis / heme biosynthetic process / embryonic digit morphogenesis / mitochondrial transport ...heme export / heme transport / heme transmembrane transporter activity / embryonic skeletal system morphogenesis / head morphogenesis / regulation of organ growth / Heme biosynthesis / heme biosynthetic process / embryonic digit morphogenesis / mitochondrial transport / blood vessel development / erythrocyte maturation / spleen development / erythrocyte differentiation / Iron uptake and transport / multicellular organism growth / intracellular iron ion homeostasis / in utero embryonic development / mitochondrial inner membrane / heme binding / mitochondrion / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.42 Å | |||||||||
![]() | Hite RK / Son Y | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1. Authors: Yeeun Son / Timothy C Kenny / Artem Khan / Kıvanç Birsoy / Richard K Hite / ![]() Abstract: Phosphatidylcholine and phosphatidylethanolamine, the two most abundant phospholipids in mammalian cells, are synthesized de novo by the Kennedy pathway from choline and ethanolamine, respectively. ...Phosphatidylcholine and phosphatidylethanolamine, the two most abundant phospholipids in mammalian cells, are synthesized de novo by the Kennedy pathway from choline and ethanolamine, respectively. Despite the essential roles of these lipids, the mechanisms that enable the cellular uptake of choline and ethanolamine remain unknown. Here we show that the protein encoded by FLVCR1, whose mutation leads to the neurodegenerative syndrome posterior column ataxia and retinitis pigmentosa, transports extracellular choline and ethanolamine into cells for phosphorylation by downstream kinases to initiate the Kennedy pathway. Structures of FLVCR1 in the presence of choline and ethanolamine reveal that both metabolites bind to a common binding site comprising aromatic and polar residues. Despite binding to a common site, FLVCR1 interacts in different ways with the larger quaternary amine of choline in and with the primary amine of ethanolamine. Structure-guided mutagenesis identified residues that are crucial for the transport of ethanolamine, but dispensable for choline transport, enabling functional separation of the entry points into the two branches of the Kennedy pathway. Altogether, these studies reveal how FLVCR1 is a high-affinity metabolite transporter that serves as the common origin for phospholipid biosynthesis by two branches of the Kennedy pathway. | |||||||||
History |
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 108.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19 KB 19 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.6 KB | Display | ![]() |
Images | ![]() | 138.3 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() ![]() | 5.6 MB 200.2 MB 200.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8uc0MC ![]() 8ubwC ![]() 8ubxC ![]() 8ubyC ![]() 8ubzC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Endogenous ligand bound FLVCR1 | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.725 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Density modified map
File | emd_42111_additional_1.map | ||||||||||||
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Annotation | Density modified map | ||||||||||||
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Density Histograms |
-Half map: Half map A
File | emd_42111_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
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Density Histograms |
-Half map: Half map B
File | emd_42111_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Human FLVCR1
Entire | Name: Human FLVCR1 |
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Components |
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-Supramolecule #1: Human FLVCR1
Supramolecule | Name: Human FLVCR1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Heme transporter FLVCR1
Macromolecule | Name: Heme transporter FLVCR1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 59.899352 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAE TPGAESSPLP LTALSPRRFV VLLIFSLYSL VNAFQWIQYS IISNVFEGFY GVTLLHIDWL SMVYMLAYVP L IFPATWLL ...String: MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAE TPGAESSPLP LTALSPRRFV VLLIFSLYSL VNAFQWIQYS IISNVFEGFY GVTLLHIDWL SMVYMLAYVP L IFPATWLL DTRGLRLTAL LGSGLNCLGA WIKCGSVQQH LFWVTMLGQC LCSVAQVFIL GLPSRIASVW FGPKEVSTAC AT AVLGNQL GTAVGFLLPP VLVPNTQNDT NLLACNISTM FYGTSAVATL LFILTAIAFK EKPRYPPSQA QAALQDSPPE EYS YKKSIR NLFKNIPFVL LLITYGIMTG AFYSVSTLLN QMILTYYEGE EVNAGRIGLT LVVAGMVGSI LCGLWLDYTK TYKQ TTLIV YILSFIGMVI FTFTLDLRYI IIVFVTGGVL GFFMTGYLPL GFEFAVEITY PESEGTSSGL LNASAQIFGI LFTLA QGKL TSDYGPKAGN IFLCVWMFIG IILTALIKSD LRRHNINIGI TNVDVKAIPA DSPTDQEPKT VMLSKQSESA I UniProtKB: Heme transporter FLVCR1 |
-Macromolecule #2: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 3 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #3: water
Macromolecule | Name: water / type: ligand / ID: 3 / Number of copies: 102 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 6.0 mg/mL | ||||||||||||||||||
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Buffer | pH: 7.5 Component:
Details: 0.01 % LMNG, 0.001 % CHS, 20 mM HEPES (pHed with KOH, pH 7.5), 150 mM KCl | ||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 297 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris X |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 53.98 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: BACKBONE TRACE / Target criteria: FSC 0.5 |
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Output model | ![]() PDB-8uc0: |